Baseline tumor-immune signatures associated with response to bempegaldesleukin (NKTR-214) and nivolumab.

Hurwitz, Michael; Cho, Daniel C.; Balar, Arjun Vasant; Curti, Brendan D.; Siefker‐Radtke, Arlene O.; Sznol, Mario; Kluger, Harriet M.; Bernatchez, Chantale; Fanton, Christie; Iacucci, Ernesto; Liu, Yi; Nguyen, Tuan; Overwijk, Willem W.; Zalevsky, Jonathan; Tagliaferri, Mary; Hoch, Ute; Diab, Adi

doi:10.1200/jco.2019.37.15_suppl.2623

Cited by 23 publications

(17 citation statements)

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“…Combination of NKTR-214 and Nivolumab was shown to achieve response rates of 53%, which correlated with high IFN-γ levels [126]. Furthermore, the accumulation of IFN-γ and CD8 + TIL in tumor tissue had been seen in favorable as well as in unfavorable tumor microenvironment.…”

Section: Increasing Effectiveness Of Ici Therapymentioning

confidence: 97%

“…TIGIT + Tregs showed higher immunosuppressive potential than their TIGITcounterparts [147]. In malignant melanoma, the co-expression of PD-L1, LAG-3, TIM-3 and TIGIT was demonstrated to induce CD8 + TILs with most exhausted phenotype [125,126]. Double blockage of PD-1 and TIGIT in melanoma led to an increased proliferation and cytokine production of CD8 + TIL and was considered to be a promising approach in immunotherapy [148].…”

Section: Other Ici In Malignant Melanomamentioning

confidence: 99%

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Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

Petrova

Arkhypov

Weber

et al. 2020

IJMS

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Although melanoma is one of the most immunogenic tumors, it has an ability to evade anti-tumor immune responses by exploiting tolerance mechanisms, including negative immune checkpoint molecules. The most extensively studied checkpoints represent cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Immune checkpoint inhibitors (ICI), which were broadly applied for melanoma treatment in the past decade, can unleash anti-tumor immune responses and result in melanoma regression. Patients responding to the ICI treatment showed long-lasting remission or disease control status. However, a large group of patients failed to respond to this therapy, indicating the development of resistance mechanisms. Among them are intrinsic tumor properties, the dysfunction of effector cells, and the generation of immunosuppressive tumor microenvironment (TME). This review discusses achievements of ICI treatment in melanoma, reasons for its failure, and promising approaches for overcoming the resistance. These methods include combinations of different ICI with each other, strategies for neutralizing the immunosuppressive TME and combining ICI with other anti-cancer therapies such as radiation, oncolytic viral, or targeted therapy. New therapeutic approaches targeting other immune checkpoint molecules are also discussed.

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Section: Increasing Effectiveness Of Ici Therapymentioning

confidence: 97%

Section: Other Ici In Malignant Melanomamentioning

confidence: 99%

Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

Petrova

Arkhypov

Weber

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…In an ongoing phase I/II study, the combination of BEMPEG with the anti-PD-1 antibody nivolumab in patients with previously untreated metastatic melanoma is being investigated. At the 2019 ASCO Annual Meeting, the data of 38 efficacy-evaluable patients were presented [10]. BEMPEG combined with nivolumab achieved an ORR of 53%, a CR in 34% of patients, and a DCR of 74%.…”

Section: Combination Of Anti-pd-1 Antibodies With Pegylated Engineerementioning

confidence: 99%

“…The most common adverse events were flu-like symptoms, rash and fatigue. Therapy had to be discontinued by 9.8% of patients due to TRAEs [10] (Table 1). In conclusion, the biomarker analyses identified baseline immune signatures that correlated with response to BEMPEG combined with nivolumab.…”

Section: Combination Of Anti-pd-1 Antibodies With Pegylated Engineerementioning

confidence: 99%

Anti-PD-1 and Novel Combinations in the Treatment of Melanoma—An Update

Gellrich

Schmitz

Beissert

et al. 2020

JCM

111

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Until recently, distant metastatic melanoma was considered refractory to systemic therapy. A better understanding of the interactions between tumors and the immune system and the mechanisms of regulation of T-cells led to the development of immune checkpoint inhibitors. This review summarizes the current novel data on the treatment of metastatic melanoma with anti-programmed cell death protein 1 (PD-1) antibodies and anti-PD-1-based combination regimens, including clinical trials presented at major conference meetings. Immune checkpoint inhibitors, in particular anti-PD-1 antibodies such as pembrolizumab and nivolumab and the combination of nivolumab with the anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody ipilimumab can achieve long-term survival for patients with metastatic melanoma. The anti-PD-1 antibodies nivolumab and pembrolizumab were also approved for adjuvant treatment of patients with resected metastatic melanoma. Anti-PD-1 antibodies appear to be well tolerated, and toxicity is manageable. Nivolumab combined with ipilimumab achieves a 5 year survival rate of more than 50% but at a cost of high toxicity. Ongoing clinical trials investigate novel immunotherapy combinations and strategies (e.g., Talimogene laherparepvec (T-VEC), Bempegaldesleukin (BEMPEG), incorporation or sequencing of targeted therapy, incorporation or sequencing of radiotherapy), and focus on poor prognosis groups (e.g., high tumor burden/LDH levels, anti-PD-1 refractory melanoma, and brain metastases).

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“…A very interesting ongoing phase 1/2 clinical trial is investigating the efficiency of an IL-2 pegylated molecule (Bempegaldesleukin) in combination with nivolumab for the treatment of melanoma, with promising primary results [32].…”

Section: High-dose Interleukin-2 (Il-2)mentioning

confidence: 99%

Nanosystems for Improved Targeted Therapies in Melanoma

Beiu

Giurcăneanu

Grumezescu

et al. 2020

JCM

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Melanoma is one of the most aggressive forms of skin cancer, with limited therapeutic options. Since its incidence has been rapidly rising in recent years, the study of new targeted therapeutic strategies has increased. The implication of nanoscience in the development of alternative targeted therapies for melanoma has multiple benefits and could significantly improve the outcome of melanoma patients. In this paper, we review the most recent progress in the field of targeted therapies, emphasizing the impact of nanoscale materials on the targeting and controlled release of anti-tumor drugs. The applications of nanomedicine in the management of melanoma are extensive and refer to sentinel lymph node mapping, chemotherapy, and RNA interference; each of these applications harboring the potential to develop efficient and personalized diagnostic techniques and therapies. Further research, especially in clinical trials, is needed to establish whether fighting melanoma on the nanoscale level represents the key to reaching a critical inflection point in mankind’s battle with metastatic melanoma.

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Baseline tumor-immune signatures associated with response to bempegaldesleukin (NKTR-214) and nivolumab.

Cited by 23 publications

References 0 publications

Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

Anti-PD-1 and Novel Combinations in the Treatment of Melanoma—An Update

Nanosystems for Improved Targeted Therapies in Melanoma

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